·
Hemophilia A (classic
hemophilia, factor VIII deficiency hemophilia) is a hereditary disorder in
which bleeding is due to deficiency of the coagulation factor VIII
·
X-linked recessive disease,
and as a rule only males are affected
·
In rare instances, female
carriers are clinically affected if their normal X chromosomes are
disproportionately inactivated. Females may also become affected if they are
the offspring of a hemophiliac father and carrier mother.
·
Severe if factor VIII:C
levels are less than 1%
·
Moderate if levels are 1–5%
·
Mild if levels are greater
than 5%.
o Clinical Findings
·
Hemophilia A is the most
common severe bleeding disorder
·
Second most common
congenital bleeding disorder ( after vWD)
·
Bleeding may occur
anywhere.
·
The most common sites of
bleeding are into joints (knees, ankles, elbows), into muscles, and from the
gastrointestinal tract.
·
Spontaneous hemarthroses
are so characteristic of severe hemophilia that they are almost diagnostic of
the disorder.
·
Patients with mild hemophilia
bleed only in response to major trauma or surgery.
·
Patients with moderately
severe hemophilia bleed in response to mild trauma or surgery, and those with
severe hemophilia bleed spontaneously.
o Laboratory Findings:
·
The partial thromboplastin
time (PTT) is prolonged
·
Pothrombin time, bleeding
time, and fibrinogen level, are normal.
·
Levels of factor VIII:C are
reduced, but measurements of von Willebrand factor are normal
·
A low platelet count should
raise a suspicion of HIV-associated immune thrombocytopenia. As HIV has become
relative common in the hemophiliacs due to previous infected blood
transfusions.
·
The finding of a reduced
factor VIII:C level will distinguish this disorder from other causes of
prolonged PTT
·
Clinically, factor VIII
hemophilia is indistinguishable from factor IX hemophilia ( Hemophilia B)
·
In cases of mild
hemophilia, the disorder needs to be distinguished from von Willebrand's
disease by VIII:A assay, which shows normal levels of factor VIII antigen in
the former.
·
Female carriers can usually
be identified by the presence of low or normal levels of factor VIII:C with
normal levels of factor VIII antigen.
·
Lve as nearly normal lives
as possible
·
Activities associated with
a risk of trauma should be avoided
·
Asprin should never be
used.
·
Standard treatment is based
on infusion of factor VIII concentrates, now heat-treated to reduce the
likelihood of transmission of HIV.
·
Recombinant factor VIII
appears safe and effective, though expensive
·
Head injuries (with or
without neurologic signs) should be emergently treated as though major bleeding
were present.
·
For mild hemophiliacs,
desmopressin acetate, may be useful in preparing for minor surgical procedures.
·
Desmopressin acetate causes
release of factor VIII:C and will raise the factor VIII:C levels two- to
threefold for several hours.
Ø
Hemophilia B (Christmas
disease, factor IX hemophilia) is a hereditary bleeding disorder due to
deficiency of coagulation factor IX.
Ø
Factor IX deficiency is
one-seventh as common as factor VIII deficiency hemophilia but is otherwise
clinically and genetically identical.
Ø
The PTT is prolonged, and
factor IX levels are reduced when measured by specific factor assays. Other
laboratory features are the same as for factor VIII hemophilia.
Ø
Factor IX hemophilia is
managed with factor IX concentrates.
Ø
Factor VIII concentrates
are ineffectual in this type of hemophilia; therefore it is imperative to
distinguish between the two.
Ø
Factor IX concentrates
contain a number of other proteins, including activated coagulating factors
that appear to contribute to a risk of thrombosis with recurrent usage of
factor IX concentrates.
Ø
Desmopressin acetate is not
useful in this disorder.
Ø
This disorder is seen
primarily among Ashkenazi Jews
Ø
Autosomal recessive.
Ø
The PTT may be markedly
prolonged, and specific assays of factor XI will show reduced levels.
Ø
Fibrinogen is absent
Ø
Both prothrombin time and
partial thromboplastin time are markedly prolonged.
Ø
These patients may have a
severe bleeding disorder similar to hemophilia. Fibrinogen is replaced with
cryoprecipitate.
·
The liver is the site of
synthesis of all the coagulation factors except factor VIII.
·
Vitamin K-dependent factors
are factors II, VII, IX, X, protein C and S.
·
Other factor synthesized in
the liver is factor V
·
Factor VII levels are the
first to decline as they have the shortest half life of 6 hours.
·
Conversely, fibrinogen
levels are remarkably well conserved.
Other
effects of liver disease on coagulation
·
Increased fibrinolysis
occurs because the liver synthesizes a2-antiplasmin (the main inhibitor of
fibrinolysis), which is responsible for the clearance of plasminogen activator.
·
Biliary tract disease may
lead to malabsorption of vitamin K
·
Congestive splenomegaly may
produce mild thrombocytopenia.
·
A variety of chronic liver
diseases cause abnormal posttranslation modification of fibrinogen with
resultant dysfibrinogenemia.
Ø
Bleeding at any site.
Ø
Excessive fibrinolysis may
lead to oozing at venipuncture sites.
Ø
Marked abnormality in
the prothrombin time (PT) than in
the partial thromboplastin time (PTT).
Ø
Early in the course of
liver disease, only the PT will become affected.
Ø
Fibrinogen levels should be
normal, and the thrombin time should be normal unless dysfibrinogenemia is
present.
Ø
The platelet count should
be normal unless production is suppressed by acute alcohol ingestion or unless
hypersplenism is present.
Ø
The peripheral blood smear
may show target cells.
Hepatic coagulopathy can
be distinguished from vitamin K deficiency only by demonstrating the failure of
vitamin K to correct the abnormal values.
Causes of prolonged PTT only Congenital factor deficiencies Contact factors Factor XII Factor XI Factor IX (hemophilia B) Factor VIII Hemophilia A Von Willebrand’s disease Anticoagulants Anti-VIII Lupus Heparin Causes of isolated prolonged
PT only Liver disease Vitamin K deficiency Warfarin therapy Factor VII deficiency Causes of prolonged PTT and
PT. Liver disease Vitamin K deficiency Disseminated intravascular
coagulation Heparin Warfarin Isolated factor deficiencies
(rare): II, V, X, I
ü
Treat the primary disease
ü
Fresh-frozen plasma is the
treatment of choice, and volume overload will limit one's ability to maintain
hemostatic factor levels.
ü
Factor IX concentrates are
contraindicated in liver disease because of their tendency to cause
disseminated intravascular coagulation.
ü
If thrombocytopenia is
present, platelet transfusion may be of some help, but platelet recovery is
usually disappointing because of hypersplenism.
v
Vitamin K plays a role in
coagulation by acting as a cofactor for the posttranslational γ-carboxylation
of zymogens II, VII, IX, and X.
v
Vitamin K is supplied in
the diet primarily in leafy vegetables and endogenously from synthesis by
intestinal bacteria.
v
Factors that contribute to
vitamin K deficiency include
v
Poor diet
v
Malabsorption
v
Broad-spectrum antibiotics
suppressing colonic flora.
v
A characteristic
setting for vitamin K deficiency is a postoperative patient who is not eating
and who is receiving antibiotics.
v
There are no specific
clinical features, and bleeding may occur at any site.
v
PT is prolonged to a
greater extent than the PTT
v
With mild vitamin K
deficiency only the PT is defective
v
Fibrinogen level, thrombin
time, and platelet count are not affected.
Subcutaneous vitamin K, and a single dose of 15 mg will
completely correct laboratory abnormalities in 12–24 hours.